Six closely related projects are proposed. (1) Human leukocyte elastase will be incubated with purified elastin from dog and human lungs. The elastin-digest peptides will be characterized by peptide-mapping and N-terminal amino acid analysis. (2) The human lung elastin-digest peptides from (1) will be fractionated by molecular-sieving chromatography, and the largest fragments will be used to raise antibodies in rabbits. The antisera will be characterized and used for immunochemical detection and quantification of elastin fragments that may be present in serum and urine of patients with chronic obstructive lung disease (COLD). Test subjects will include those with advanced COLD, subclinical COLD and pneumonias (with and without underlying COLD). Controls will include healthy individuals and those without detectable lung disease but with other connective tissue pathology. COLD patients will be monitored in a longitudinal study and the findings correlated with disease progress and infection. Patients will be classified by assessment of lung volume, air flow rates, diffusing capacity, lung compliance and blood gases. Controls will be screened by plethysmography and flow-volume loops. Analysis of results will include correlations with serum trypsin-inhibiting capacity, smoking history and drugs received. (3) In a parallel animal model, dog lung elastin will be digested with porcine pancreatic elastase and rabbit antibodies will be raised to these digest fragments. Serum and urine of dogs will be tested immunochemically for elastin fragments from 1/2 hr. to 72 hr. after endotracheal instillation of the porcine enzyme. Results will be correlated with lesion severity at necropsy. The effect of peptide chloromethyl ketones and other elastase inhibitors can also be tested in this animal model. (4) Leukocyte elastase will be instilled into isolated, perfused dog lungs which will then be examined microscopically for emphysema-like changes. Indirect immuno-enzyme staining (LM and EM) will be used to study distribution and binding of the enzyme in the tissues. (5) The effect of leukocyte elastase and chymotrypsin on surface activity of human surfactant "core-lipoprotein" will be measured with a surface balance. (6) Leukocyte proteases will be tested for degradation of lung glycoproteins.